gaba能调节黑腹果蝇特定行为的药理学证据。

S. Leal, W. Neckameyer
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引用次数: 62

摘要

我们已经确定了黑腹果蝇的几种GABA能调节行为,采用药理学方法在体内破坏GABA转运蛋白的功能。用GABA转运抑制剂dl -2,4-二氨基丁酸(DABA)或R,S-nipecotic acid (NipA)对成年雌性果蝇进行全身治疗,会导致运动活动减弱,地向性缺陷,并诱发抽搐行为,继发性翻正反射丧失。药理学证据表明,观察到的行为表型与GABA转运蛋白功能和GABA能活性的破坏有关。GABA再摄取抑制剂对运动活动的影响是剂量依赖性的,药理学上是不同的,并且与它们在哺乳动物系统中的已知作用相似。双管碱(bicuculline, BIC)是一种GABA受体拮抗剂,可抑制哺乳动物GABA能活性,经DABA和nipa处理的果蝇可恢复正常的运动活动和翻正反射。这些行为的恢复也可以通过加巴喷丁(一种与哺乳动物gaba能系统相互作用的抗惊厥剂)的共同施用来实现。最后,行为效应是选择性的,因为其他特定的行为,如进食活动和雌性的性接受性不受影响。在离体果蝇突触质膜囊泡上进行的相关药理分析表明,[3H]-GABA具有高亲和力和饱和摄取机制;进一步对DABA和NipA的竞争性抑制研究表明它们能够抑制[3H]-GABA转运。果蝇中实验可获得的GABA转运体与哺乳动物的转运体共享保守的药理学特性,这导致了GABA调节的特定行为的鉴定。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Pharmacological evidence for GABAergic regulation of specific behaviors in Drosophila melanogaster.
We have identified several GABAergic-modulated behaviors in Drosophila melanogaster by employing a pharmacological approach to disrupt GABA transporter function in vivo. Systemic treatment of adult female flies with the GABA transport inhibitors DL-2,4-diaminobutyric acid (DABA) or R,S-nipecotic acid (NipA), resulted in diminished locomotor activity, deficits in geotaxis, and the induction of convulsive behaviors with a secondary loss of the righting reflex. Pharmacological evidence suggested that the observed behavioral phenotypes were specific to disruption of GABA transporter function and GABAergic activity. The effects of GABA reuptake inhibitors on locomotor activity were dose dependent, pharmacologically distinct, and paralleled their known effects in mammalian systems. Recovery of normal locomotor activity and the righting reflex in DABA- and NipA-treated flies was achieved by coadministration of bicuculline (BIC), a GABA receptor antagonist that supresses GABAergic activity in mammals. Recovery of these behaviors was also achieved by coadministration of gabapentin, an anticonvulsant agent that interacts with mammalian GABAergic systems. Finally, behavioral effects were selective because other specific behaviors such as feeding activity and female sexual receptivity were not affected. Related pharmacological analyses performed in vitro on isolated Drosophila synaptic plasma membrane vesicles demonstrated high affinity, saturable uptake mechanisms for [3H]-GABA; further competitive inhibition studies with DABA and NipA demonstrated their ability to inhibit [3H]-GABA transport. The existence of experimentally accessible GABA transporters in Drosophila that share conserved pharmacological properties with their mammalian counterparts has resulted in the identification of specific behaviors that are modulated by GABA.
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